Age- and stimulus-dependent changes in anxiety-related behaviour of transgenic mice with GR dysfunction.

Transgenic mice expressing antisense directed against glucocorticoid receptor (GR) mRNA were used for a longitudinal study on the effects of hypothalamic-pituitary-adrenocortical dysfunction on anxiety-related behaviour and locomotor activity. Compared with age-matched controls and 5-week-old transgenic animals, 13- and 36-week-old transgenic mice made significantly more entries into and spent significantly more time on the open arms of the elevated plus-maze thereby indicating reduced basal anxiety. In contrast, time spent in the central area of the open field was significantly reduced in transgenic animals indicating an enhanced anxiety under conditions of increased stress. Locomotor activity did not differ between transgenic and control animals. Our results indicate that behavioural changes in transgenic mice differ according to the age of the animals and the behavioural paradigm used. Transgenic animals with an impaired GR function may be of help in studying the interaction of ageing, GR function and the development of behavioural abnormalities.